Sonography of Complex Gallbladder Disease
Author:
Sharlene A. Teefey, M.D.
Objectives: Upon the completion of this CME article, the reader will be able to:
1.
List the risk factors for gangrenous cholecystitis and describe the sonographic
findings seen with this disorder.
2.
Categorize the types of gallbladder perforation and the sonographic patterns of pericholecystic fluid.
3.
Describe the etiology of acalculous cholecystitis and define the sonographic findings
seen with this disorder.
4.
Describe the etiology of emphysematous cholecystitis and define the sonographic
findings seen with this disorder.
Introduction:
Recent studies have reported new trends in the patients who develop acute
cholecystitis, including a greater incidence in patients who are elderly or diabetic. There has
also been an increased incidence of acalculous and gangrenous cholecystitis. This article will
review the pathogenesis and the clinical and sonographic features of gangrenous, acalculous,
and emphysematous cholecystitis.
Gangrenous cholecystitis
Gangrenous cholecystitis occurs in approximately 20% of cases of acute
cholecystitis. The incidence is equal in men and women. The majority of patients are
elderly; however, cases have been reported in younger patients who are immunosuppressed,
have a malignancy, or are on steroids. In the elderly population, atherosclerosis and diabetes
mellitus are important predisposing factors. The mortality rate for gangrenous cholecystitis
is 5% to 10%, and perforation occurs in approximately 10% of cases. While the definition
of gangrenous cholecystitis is somewhat variable in the literature, it is considered present
when there is histologic evidence of coagulative necrosis (surface ulceration or transmural
necrosis) and acute and or chronic inflammation. Gallstones are present in most patients.
The pathogenesis begins with impaction of a stone in the cystic duct, followed by the
development of bile salt that is more concentrated than normal, which then incites a
chemical inflammatory reaction. As mucus production continues, the gallbladder becomes
distended, leading to ischemia (a lack of blood flow), necrosis (cell death), and perforation
within one to seven days after the onset of symptoms.
The signs and symptoms of gangrenous cholecystitis may mimic those of
uncomplicated acute cholecystitis (nausea, vomiting, right upper quadrant pain and
tenderness, fever, and leukocytosis or elevated white blood cell count), but can also be
absent. In our series of 25 patients with gangrenous cholecystitis, at initial presentation, 50%
were afebrile, 30% had a nontender abdomen, 20% had no abdominal pain, and 15% had a
normal white blood cell count. Two of these signs and/or symptoms were absent in 30% of
patients and three or more were absent in 10% (Teefey, unpublished data).
Several sonographic findings have been described in patients with gangrenous
cholecystitis, including absence of a sonographic Murphy sign, intraluminal membranes, wall
irregularity and intramural perforation, gallbladder wall striations, and peri-cholecystic fluid
collections. The absence of a sonographic Murphy sign is an important finding, which may
occur in up to 67% of patients. The Murphy sign is absent due to necrosis of the visceral
afferent nerve fibers supplying the gallbladder. Intraluminal membranes are probably due to
a fibrinous exudate or sloughed, necrotic mucosa (figure 1). This finding may be simulated
by thick tenacious mucus within the gallbladder lumen or by a multi-septate gallbladder.
Irregularity of the gallbladder wall and intramural perforation is due to wall hemorrhage,
microabscess formation, ulceration, and necrosis. Striated gallbladder wall thickening
appears sonographically as multiple hypoechoic layers separated by echogenic zones (figure
2). We often observed this finding prior to perforation. In our series of 25 patients with
gangrenous cholecystitis, gallbladder wall striations were observed in 10 cases, whereas
intraluminal membranes and wall irregularity were observed in only 1 case each. Gallbladder
wall striations appear to be a frequent, early sign of gangrenous cholecystitis. While striated
gallbladder wall thickening is associated with gangrenous cholecystitis, it has also been
identified in patients with edema and or inflammation of the wall unrelated to gallbladder
disease including those with hepatitis, portal hypertension, right heart failure, renal failure,
ascites, hypoalbuminemia, pancreatitis, and obstruction of the lymphatic and or venous
drainage of the gallbladder. Thus, although this finding is nonspecific, in the setting of acute
cholecystitis, striations suggest gangrenous changes in the gallbladder wall.
Gallbladder wall perforation usually occurs in the fundus because the cystic artery
branches are end arteries so fresh blood reaches the fundus last. Three types of gallbladder
wall perforation may occur: acute, subacute, and chronic. Acute, free peritoneal perforation
is rare and results in bile peritonitis. Subacute perforation with peri-cholecystic abscess
formation is the most common type. Chronic gallbladder wall perforation with
cholecystoenteric fistula formation is unusual. Fistulous communication occurs most
frequently with the duodenum and or hepatic flexure (figure 3). In our series of 25 patients
with gangrenous cholecystitis, sonography revealed two patterns of peri-cholecystic fluid
collections. Type I fluid collections were thin, anechoic crescent-shaped collections adjacent
to the gallbladder wall. Type II fluid collections were large, round, and irregular in shape and
complex (thick walls, internal debris, or septations). The gallbladder may or may not be
identifiable as a separate structure. Type I fluid collections were not typically associated with
gallbladder perforation whereas type II fluid collections were nearly always associated with
gallbladder wall perforation and abscess formation.
Acute Acalculous Cholecystitis
Acute acalculous cholecystitis occurs in 10%-14% of cases of acute cholecystitis. It
is more common in men than in women (3:1) and usually occurs in patients 50 to 65 years of
age. The mortality rate averages 40% and the incidence of perforation is 15%. Predisposing
risk factors include previous surgery or trauma, ICU admission, mechanical ventilation, one
or more episodes of hypoventilation, prolonged fasting or total parenteral nutrition (TPN)
usage, and narcotic use.
The pathogenesis of acalculous cholecystitis is multifactorial and includes ischemia,
gallbladder stasis, sepsis, and toxins. Ischemia occurs due to hypotension or hypovolemia,
especially in postoperative or post-trauma patients or in patients with severe pancreatitis or
burns. Atherosclerosis has also been implicated as a cause of ischemia in acute acalculous
cholecystitis. In one study, the authors reviewed their seven-year experience with acute
acalculous cholecystitis and found that 75% of cases occurred in older men who were
healthy, except for atherosclerotic vascular disease. Gallbladder stasis, which occurs in the
setting of prolonged fasting, parenteral nutrition, and narcotic use, is another predisposing
factor. As bile salts become concentrated, chemical inflammation of the gallbladder wall
ensues, leading to cholecystitis. Sepsis also is hypothesized as a cause for acute acalculous
cholecystitis. Finally, bacterial endotoxins may activate factor XII dependent pathways,
injuring blood vessels in the gallbladder wall.
Signs and symptoms of acute acalculous cholecystitis may be similar to those in
uncomplicated acute cholecystitis, but may be masked by narcotics, postoperative incisional
pain, or a decreased level of consciousness. In one report, only 37% of patients were febrile,
70% had a leukocytosis, and 56% had right upper quadrant pain. In addition, symptoms
may be non-localizing, and patients may present with an isolated fever or diffuse abdominal
pain.
Several reports have described sonographic findings associated with acute acalculous
cholecystitis, including gallbladder wall thickening, lumen distension, peri-cholecystic fluid, a
positive sonographic Murphy sign, lack of gallbladder contraction in response to
cholecystokinin, and the presence of sludge. However, most of these findings are
nonspecific and are not very sensitive in diagnosing acute acalculous cholecystitis.
Gallbladder wall thickening may be normal in 15% to 30% of cases, especially early in the
course of the disease (figure 4). Furthermore, gallbladder wall thickening may be due to
several other etiologies, including hypoalbuminemia, ascites, right heart failure, renal failure,
and liver disease. Gallbladder distension may not be present when prior inflammation and
fibrosis limit the gallbladder’s ability to distend. If the etiology of acute acalculous
cholecystitis is ischemia, distension of the gallbladder may also be absent. Alternatively,
gallbladder distension may be present in the setting of prolonged fasting, parenteral
nutrition, diabetes mellitus, prior vagotomy, or distal common bile duct obstruction. Pericholecystic fluid is not sensitive in diagnosing acute acalculous cholecystitis and may be
absent in the early stages of inflammation. The presence of peri-cholecystic fluid also is
nonspecific and may occur in patients with peptic ulcer disease, pancreatitis, ascites, or
peritonitis. A positive sonographic Murphy sign, while very specific for acute cholecystitis, is
frequently absent in the presence of gangrenous changes or may be masked by narcotic use
and postoperative pain. The presence of gallbladder sludge is nonspecific and may be
observed in prolonged fasting states and parenteral nutrition use. Finally, the inability of the
gallbladder to contract in response to cholecystokinin has been reported in postoperative
patients with no evidence of gallbladder disease.
Emphysematous cholecystitis
Emphysematous cholecystitis occurs in approximately 1% of cases of acute
cholecystitis. It is more common in men than in women (3:1) and usually occurs in patients
50 to 70 years of age. Diabetes mellitus is present in up to 40% of cases, and cholelithiasis is
present in up to 50%. The mortality rate is approximately 15%. Gangrenous changes occur
in approximately 75% of cases, with progression to perforation in 20%. Emphysematous
cholecystitis is due to ischemia from cystic artery or arteriolar narrowing. Secondary
infection occurs from gas-forming organisms, including Clostridium welchii, E. coli,
staphylococcus, or anaerobic streptococcus.
Signs and symptoms of emphysematous cholecystitis may mimic those of
uncomplicated acute cholecystitis or may be unusually severe, with right upper quadrant pain
and sepsis. However, in two studies, 30%-50% of patients were afebrile, only 50% had an
elevated white blood cell count, and abdominal tenderness was frequently absent.
Several sonographic features have been described in patients with emphysematous
cholecystitis, including intramural and intraluminal gas. Intramural gas will cause the
gallbladder wall to be hyperechoic with posterior reverberation producing comet tail or ring
down artifact (figure 5). However, these sonographic findings may be caused by other
pathologic conditions. Adenomyomatosis may cause comet tail artifacts in the gallbladder
wall that simulate the appearance of intramural gas. A porcelain gallbladder may also
produce an echogenic wall, but there is no distal reverberation, which aids in differentiating
this condition from emphysematous cholecystitis. Intraluminal gas may produce tiny echoic
foci with posterior reverberation that rise toward the nondependent wall. Floating
cholesterol crystals may simulate the appearance of intraluminal gas, however, intraluminal
gas rises to the nondependent portion of the gallbladder, whereas cholesterol crystals settle
in the dependent portion of the gallbladder. In addition, intraluminal gas may be due to
multiple other etiologies including biliary-enteric anastomoses or fistulae or an incompetent
sphincter of Oddi. Clinical history is important in distinguishing these entities from
emphysematous cholecystitis.
In summary, gangrenous cholecystitis, acalculous cholecystitis, and emphysematous
cholecystitis are entities that are increasing in incidence, have a high morbidity and mortality
rate, and may have an atypical and often subtle clinical presentation. Sonographic findings,
when observed, must be interpreted within the context of the patient’s overall clinical status,
given the low specificity and sensitivity of many of the findings.
Figures:
1
Gangrenous gallbladder with intraluminal membranes from sloughed mucosa
2
Striated gallbladder wall thickening from pancreatitis
3
Gangrenous gallbladder with perforation into the liver
4
Acalculous cholecystitis with normal wall thickness and sludge
5
Emphysematous cholecystitis with intramural and intraluminal air
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2.
Roslyn J, Busuttil RW. Perforation of the gallbladder: A frequently mismanaged
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3.
Madrazo BL, Francis I, Hricak H, et al. Sonographic findings in perforation of the
gallbladder. AJR 139:491-496, 1982.
4.
Teefey SA, Baron RL, Radke HM et al. Gangrenous cholecystitis: New observations
on sonography. J Ultrasound Med 10:603-606, 1991.
5.
Simeone JF, Brink JA, Mueller PR et al. The sonographic diagnosis of acute
gangrenous cholecystitis: Importance of the Murphy sign. AJR 152:289-290, 1989.
6.
Isch JH, Finneran JC, Nahrwold DL. Perforation of the gallbladder. Am J
Gastroenterol 55:451-458, 1971.
7.
Strohl EL, Diffenbaugh WG, Baker JH et al. Gangrene and perforation of the
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8.
Jeffrey RB, Laing FC, Wong W et al. Gangrenous cholecystitis: Diagnosis by
ultrasound. Radiology 148:219-221, 1983.
9.
Cohan RH, Mahoney BS, Bowie JD et al. Striated intraluminal gallbladder lucencies
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10.
Teefey SA, Baron RL, Bigler SA. Sonography of the gallbladder: Significance of
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11.
Fletcher AG, Ravdin IS. Perforation of the gallbladder. Am J Surg 81:178-185, 1951.
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13.
Glenn F, Becker CG: Acute acalculous cholecystitis. Ann Surg, 195:31-136, 1982.
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Johnson LB: The importance of early diagnosis of acute acalculous choleystitis.
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15.
Fox MS, Wilk PJ, Weissman HS, et al: Acute acalculous cholecystitis. Surg, Gyn &
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Long TN, Heimbach, DM, Carrico CJ: Acalculous cholecystitis in critically ill
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17.
Savoca PE, Longo WE, Zucker KA, et al: The increasing prevalence of acalculous
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critically ill. Am Surg 60(5):335-338,1994.
19.
Frazee RC, Nagorney DM, Mucha P: Acute acalulous cholecystitis. Mayo Clin Proc,
64:163-167, 1989.
20.
Boland GW, Slater G, Lu DS, et al. Prevalence and significance of gallbladder
abnormalities seen on sonography in intensive care unit patients. AJR,174:973-977,
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21.
Boland GW, Lee MJ, Leung J, et al. Percutaneous cholecystostomy in critically ill
patients: early response and final outcome in 82 patients. AJR 163:339-342, 1994.
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Shuman WP, Rogers JV, Rudd TG, et al: Low sensitivity of sonography and
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23.
Blankenberg F, Wirth R, Jeffrey RB, et al: Computed tomography as an adjunct to
ultrasound in the diagnosis of acute acalculous cholecystitis. Gastrointest Radiol
16:149-153, 1991.
24.
Cohen SM, Kurtz AB: Biliary sonography. Radiol Clin North Am 29:1171-1198,
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25.
Raduns K, McGahan JP, Beal S: Cholecystokinin sonography: Lack of utility in
diagnosis of acute acalculous cholecystitis. Radiology 175:463-466, 1990.
26.
Nyberg DA, Laing FC. Ultrasonographic findings in peptic ulcer disease and
pancreatitis which simulate primary gallbladder disease. J Ultrasound Med, 2:303,
1983.
27.
Mentzer RM, Golden GT, Chandler JF, et al: A comparative appraisal of
emphysematous cholecystitis. Am J Surg 129:10-15, 1975.
28.
Lorenz RW, Steffen HM: Emphysematous cholecystitis: Diagnostic problems and
differential diagnosis of gallbladder gas accumulations. Hepato-gastroenterol 37:103106, 1990.
29.
Brandon JC, Glick SN, Teplick SK, et al: Emphysematous cholecystitis: Pitfalls in its
plain film diagnosis. Gastrointest Radiol 13:33-36, 1988.
30.
Gill KS, Chapman AH, Weston MJ. The changing face of emphysematous
cholecystitis. Br J Rad 70:986-991, 1997.
31.
Franquet T, Bescos JM, Barberena J, et al: Accoustic artifacts and reverberation
shadows in gallbladder sonograms: their cause and clinical implications. Gastrointest
Radiol 15:223-228, 1990.
32.
Bloom RA, Libson E, Lebensart PD, et al: The ultrasound spectrum of
emphysematous cholecystitis. J Clin Ultrasound 17:251-256, 1989.
33.
Parulekar SG: Sonographic findings in acute emphysematous cholecystitis.
Radiology 145:117-119, 1982.
34.
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sonographic sign of emphysematous cholecystitis. Am J Radiol 150:575-577, 1988.
35.
Lafortune M, Gariepy G, Dumont A, et al: The v-shaped artifact of the gallbladder
wall. Am J Radiol 147:505-508, 1986.
36.
Raghavendra BN, Subramanyam BR, Balthazar EJ, et al: Sonography of
adenomyomatosis of the gallbladder: Radiologic-pathologic correlation, Radiology
146:747-752, 1983.
37.
Kane RA, Jacobs R, Katz J, et al: Porcelain gallbladder: Ultrasound and CT
appearance. Radiology 152:137-141, 1984.
About the Author:
Sharlene A. Teefey, M.D. is currently an Associate Professor of Radiology at the
Mallinckrodt Institute of Radiology at Washington University School of Medicine in St.
Louis Missouri. She is a member of numerous societies and organizations including the
American College of Radiology, the Society of Radiologists in Ultrasound, and the American
Institute of Ultrasound in Medicine.
She is a reviewer of manuscripts for Radiology, the American Journal of Roentgenology, and
Radiographics. She has more than 45 publications in peer review medical journals and has
been a speaker at numerous institutions and conferences across the country.
Examination:
1.
Which of the following statements is (are) true regarding gangrenous cholecystitis?
A.
It occurs in approximately 40% of cases of acute cholecystitis.
B.
The majority of patients are very young; however, cases have been reported
in elderly patients who are immunosuppressed or are on steroids.
C.
The mortality rate for gangrenous cholecystitis is 5% to 10%, and perforation
occurs in approximately 10% of cases.
D.
Gallstones are absent in most patients.
E.
B & C above are true.
2.
The pathogenesis of gangrenous cholecystitis begins with impaction of a stone in the
A.
sphincter of Oddi.
B.
cystic duct.
C.
hepatic duct
D.
pyloric sphincter
E.
tubal sphincter
3.
The signs and symptoms of gangrenous cholecystitis may mimic those of
uncomplicated acute cholecystitis, which includes
A.
nausea, vomiting, and fever
B.
left upper quadrant pain and tenderness
C.
a decreased white blood cell count
D.
all of the above
E.
only A & B above
4.
Several sonographic findings have been described in patients with gangrenous
cholecystitis, including
A.
absence of a sonographic Murphy sign.
B.
intraluminal membranes and wall irregularity.
C.
gallbladder wall striations and peri-cholecystic fluid collections.
D.
all of the above.
E.
only B & C above.
5.
Which of the following statements is (are) true regarding sonography of gangrenous
cholecystitis?
A
The presence of a sonographic Murphy sign is an important finding, which
occurs in over 85% of patients.
B.
Intraluminal membranes are probably due to a fibrinous exudate or sloughed,
necrotic mucosa.
C.
Irregularity of the gallbladder wall and intramural perforation is due to
necrosis of the visceral afferent nerve fibers supplying the gallbladder.
D.
E.
Striated gallbladder wall thickening appears sonographically as multiple
hyperechoic layers separated by echodense zones.
all of the above are true.
6.
While striated gallbladder wall thickening is associated with gangrenous cholecystitis,
it has also been identified in patients with edema and or inflammation of the wall
unrelated to gallbladder disease including those with
A.
hepatitis and pancreatitis
B.
left heart failure and hyperalbuminemia
C.
renal failure and obstruction of the lymphatic and or venous drainage of the
gallbladder
D.
A & C above
E.
B & C above
7.
Three types of gallbladder wall perforation may occur: acute, subacute, and chronic.
A.
Acute, free peritoneal perforation is the most common but rarely results in
bile peritonitis.
B.
Subacute perforation with peri-cholecystic abscess formation is the most rare
type.
C.
Chronic gallbladder wall perforation with cholecystoenteric fistula formation
is unusual.
D.
all of the above
E.
only A & C above
8.
In the author’s series of 25 patients with gangrenous cholecystitis, sonography
revealed two patterns of peri-cholecystic fluid collections.
A.
Type I fluid collections were thin, anechoic crescent-shaped collections
adjacent to the gallbladder wall.
B.
Type II fluid collections were large, round, and irregular in shape and
complex with thick walls, internal debris, or septations.
C.
Type I fluid collections were not typically associated with gallbladder
perforation
D.
Type II fluid collections were nearly always associated with gallbladder wall
perforation and abscess formation.
E.
All of the above.
9.
Acute acalculous cholecystitis
A.
occurs in 10%-14% of cases of acute cholecystitis.
B.
is more common in women than in men (3:1)
C.
usually occurs in patients 20 to 35 years of age.
D.
A & B above.
E.
B & C above.
10.
Predisposing risk factors for acute acalculous cholecystitis include
A.
previous surgery or trauma
B.
admission to the ICU
C.
mechanical ventilation
D.
prolonged fasting or total parenteral nutrition (TPN) usage
E.
all of the above.
11.
The pathogenesis of acalculous cholecystitis is multifactorial and includes
A.
ischemia and gallbladder stasis
B.
peptic ulcer disease
C.
sepsis and toxins.
D.
A & B above.
E.
A & C above.
12.
Which of the following statements is (are) true?
A.
Gallbladder stasis occurs in the setting of hypertension.
B.
Gallbladder stasis occurs in the setting of prolonged fasting.
C.
Gallbladder stasis occurs in the setting of narcotic use.
D.
all of the above.
E.
only B & C above
13.
The sonographic findings associated with acute acalculous cholecystitis include
A.
gallbladder wall thinning
B.
peri-cholecystic fluid and the presence of sludge
C.
gallbladder contraction in response to cholecystokinin
D.
all of the above.
E.
only B & C above.
14.
Which of the following statements is (are) true?
A.
Gallbladder distension may not be present when prior inflammation and
fibrosis limit the gallbladder’s ability to distend.
B.
Peri-cholecystic fluid is very sensitive in diagnosing acute acalculous
cholecystitis and is nearly always present in the early stages of inflammation.
C.
The presence of peri-cholecystic fluid is also very specific and is not really
seen with other disorders.
D.
All of the above.
E.
Only A & B above.
15.
Gallbladder distension may be present in the setting of
A.
prolonged fasting or total parenteral nutrition.
B.
diabetes mellitus or prior vagotomy.
C.
proximal common bile duct obstruction.
D.
A & B above.
E.
B & C above.
16.
Emphysematous cholecystitis
A.
occurs in approximately 10% of cases of acute cholecystitis.
B.
is more common in women than in men (3:1)
C.
usually occurs in patients 50 to 70 years of age.
D.
all of the above.
E.
only A & B above.
17.
Emphysematous cholecystitis is due to ischemia from
A.
B
C.
D.
E.
cystic artery or arteriolar narrowing.
cystic artery or arteriolar dilation.
splenic artery or arteriolar narrowing.
splenic artery or arteriolar dilation.
gastric artery or arteriolar narrowing.
18.
Several sonographic features have been described in patients with emphysematous
cholecystitis. Which of the following statements is (are) true?
A.
Intramural gas will cause the gallbladder wall to be hypoechoic with anterior
reverberation producing comet tail artifact.
B.
Adenomyomatosis may cause comet tail artifacts in the gallbladder wall that
simulate the appearance of intramural gas.
C.
A porcelain gallbladder may produce an echogenic wall and this is confirmed
by the presence of distal reverberation
D.
all of the above.
E.
only B & C above.
19.
Sonographically, floating cholesterol crystals may simulate the appearance of
intraluminal gas, however,
A.
intraluminal gas settles in the dependent portion of the gallbladder
B.
cholesterol crystals rise to the nondependent portion of the gallbladder
C.
intraluminal gas rises to the nondependent portion of the gallbladder
D.
cholesterol crystals remain evenly dispersed within the gallbladder.
E.
none of the above
20.
Intraluminal gas in the gallbladder may be due to
A.
emphysematous cholecystitis.
B.
biliary-enteric anastomoses or fistulae
C.
an incompetent sphincter of Oddi.
D.
all of the above.
E.
only A & C above.